Polymer fiber tubular structure having kinking resistance

ABSTRACT

An apparatus for forming a tubular structure from a liquefied polymer, the apparatus comprising: (a) a dispenser for dispensing the liquefied polymer; (b) a precipitation electrode being at a first potential relative to the dispenser, the precipitation electrode being designed and constructed for generating a polymeric shell thereupon; and (c) a mechanism for increasing a local density of the polymeric shell in a plurality of predetermined sub-regions of the polymeric shell, thereby to provide a tubular structure having an alternating density in a longitudinal direction.

RELATED PATENT APPLICATION

This application is a National Phase Application of PCT/IL02/00219International Filing Date 19 Mar. 2002, which claims priority from U.S.patent application Ser. No. 09/982,017 filed 19 Oct. 2001, nowabandoned, which claims priority from U.S. Provisional PatentApplication No. 60/276,956 filed 20 Mar. 2001 and U.S. ProvisionalPatent Application No. 60/256,323 filed on Dec. 19, 2000.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to a method and apparatus formanufacturing tubular structures via electrospinning and, moreparticularly, to a method and apparatus for manufacturing a polymerfiber tubular structure having improved kinking resistance. The presentinvention further relates to tubular structures having improved kinkingresistance.

In many medical and industrial applications, tubular structures madefrom polymer fibers are used as, e.g., vascular prostheses, shunts andthe like. Production of polymer fiber tubular structures is particularlydifficult when such tubular structures are required to have radialtensile strength sufficient to resist tearing and collapse in responseto a pulsating pressure while at the same time maintain several elasticproperties, such as the ability to bend without breaking and withoutkinking, in order to allow conformation to a complex geometry.

When an elastic tubular product bends, it experience a finite force ontoa small surface area, hence the stress concentration at the bendingpoint is high. Consequently, the tubular product is kinked, i.e., iteither undergoes destruction, or bends with inner lumen collapse.

A typical method known in the art to prevent such a collapse is tosupport the surfaces of the tubular product by rigid circular members sothat the product is made of alternating elastic and rigid longitudinalsections. Upon axial deformations, the elastic members can freelyoperate by tension-compression within the limits admissible by the agentelastic properties, while at the same time, development of radialdeformations is limited by the presence of the rigid elements.

Radial support of tubular product can be done in more than one way. Forexample, tube corrugation provides alternating sections with differingdiameter but permanent wall thickness. In this case, required rigidityis achieved at the expense of a plurality of wall members oriented at anangle which is close to 90° relative to the tube central axis. Anothermethod is to reinforce an inner or outer wall of an elastic tube, by arigid spiral pattern made of steel wire or polymer thread of anappropriate diameter. This type of structure can be also found inphysiological systems such as the tracheal and the bronchial of therespiratory system, were rigid cartilage-tissue rings are interconnectedby the elastic connective tissue.

In the vascular system, blood vessels possess integrity of uniquebiomechanical properties. Of particular importance is the resistance ofthe vessel to inner lumen collapse upon sharp “corners”, which ensuresnormal blood supply.

Production of tubular fibrous products, including artificial bloodvessels, is described in various patents inter alia using the techniqueof electrospinning of liquefied polymer, so that tubular productscomprising polymer fibers are obtained. Electrospinning is a method forthe manufacture of ultra-thin synthetic fibers, which reduces the numberof technological operations and increases the stability of properties ofthe product being manufactured.

The process of electrospinning creates a fine stream or jet of liquidthat upon proper evaporation of a solvent or liquid to solid transitionstate yield a non-woven structure. The fine stream of liquid is producedby pulling a small amount of polymer solution through space viaelectrical forces. More particularly, the electrospinning processinvolves the subjection of a liquefied polymer substance into anelectric field, whereby the liquid is caused to produce fibers that aredrawn by electric forces to an electrode, and are, in addition,subjected to a hardening procedure. In the case of liquid which isnormally solid at room temperature, the hardening procedure may be merecooling; however other procedures such as chemical hardening(polymerization) or evaporation of solvent may also be employed. Theproduced fibers are collected on a suitably located sedimentation deviceand subsequently stripped of it.

Artificial vessels made by electrospinning have a number of vitalcharacteristics, including the unique fiber microstructure, in many wayssimilar to that of the natural muscular tissue, high radial complianceand good endothelization ability. However, an artificial vesselfabricated using conventional electrospinning does not withstandkinking, and further reinforcement of the final product is necessary.

The inner surface of blood vessel prosthesis must be completely smoothand even so as to prevent turbulence during blood flow and relatedthrombogenesis. This feature prevents the employment of tubecorrugation, since such structure affects the blood flow and may causethrombogenesis. In addition, the vessel rigid members must ensure radialcompliance and, if possible, have fiber structure and porosity similarto that of the basic material of the prosthesis wall. Still in addition,the rigid members should under no conditions be separated from theelastic portions of the prosthesis. On the other hand, in the vascularsystem, application of various adhesives is highly undesirable. Hence,the above mentioned techniques, to prevent collapse of the vessel lumenare inapplicable.

There is thus a widely recognized need for, and it would be highlyadvantageous to have, a method and apparatus for manufacturing tubularstructures, and particularly vascular prostheses, devoid of the abovelimitations.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided anapparatus for forming a tubular structure from a liquefied polymer, theapparatus comprising: (a) a dispenser for dispensing the liquefiedpolymer; (b) a precipitation electrode being at a first potentialrelative to the dispenser, the precipitation electrode being designedand constructed for generating a polymeric shell thereupon; and (c) amechanism for increasing a local density of the polymeric shell in aplurality of predetermined sub-regions of the polymeric shell, therebyto provide a tubular structure having an alternating density in alongitudinal direction.

According to further features in preferred embodiments of the inventiondescribed below the mechanism for increasing the local density comprisesa pressing mechanism.

According to still further features in the described preferredembodiments the mechanism for increasing the local density comprises aplurality of rollers spaced apart from one another.

According to still further features in the described preferredembodiments the mechanism for increasing the local density comprises aspiral pattern.

According to still further features in the described preferredembodiments the mechanism for increasing the local density comprises arigid irregular pattern.

According to still further features in the described preferredembodiments the dispenser is operable to move along the precipitationelectrode.

According to still further features in the described preferredembodiments the apparatus further comprising a reservoir for holding theliquefied polymer.

According to still further features in the described preferredembodiments the apparatus further comprising a subsidiary electrodebeing at a second potential relative to the dispenser, and being formodifying an electric field generated between the precipitationelectrode and the dispenser.

According to still further features in the described preferredembodiments the subsidiary electrode serves for reducingnon-uniformities in the electric field.

According to still further features in the described preferredembodiments the subsidiary electrode serves for controlling fiberorientation of the tubular structure formed upon the precipitationelectrode.

According to still further features in the described preferredembodiments the subsidiary electrode is operative to move along theprecipitation electrode.

According to still further features in the described preferredembodiments the subsidiary electrode is tilted at angle with respect tothe precipitation electrode.

According to still further features in the described preferredembodiments the apparatus further comprising a mechanism forintertwining at least a portion of a plurality of polymer fibersdispensed by the dispenser, so as to provide at least one polymer fiberbundle moving in a direction of the precipitation electrode.

According to still further features in the described preferredembodiments the mechanism for intertwining at least a portion of theplurality of polymer fibers comprises a system of electrodes, beinglaterally displaced from the dispenser, being at a third potentialrelative to the dispenser and capable of providing an electric fieldhaving at least one rotating component around a first axis definedbetween the dispenser and the precipitation electrode.

According to still further features in the described preferredembodiments the system of electrodes includes at least one rotatingelectrode, operable to rotate around the first axis.

According to still further features in the described preferredembodiments the dispenser and the at least one rotating electrode areoperative to independently move along the precipitation electrode.

According to still further features in the described preferredembodiments the dispenser and the at least one rotating electrode areoperative to synchronically move along the precipitation electrode.

According to another aspect of the present invention there is provided amethod of forming a tubular structure from a liquefied polymer, themethod comprising: (a) via electrospinning, dispensing the liquefiedpolymer from a dispenser in a direction of a precipitation electrode,hence forming polymeric shell; and (b) increasing a local density of thepolymeric shell in a plurality of predetermined sub-regions of thepolymeric shell, thereby providing a tubular structure having analternating density in a longitudinal direction.

According to further features in preferred embodiments of the inventiondescribed below, the method further comprising independently repeatingthe steps (a) and (b) at least once.

According to still further features in the described preferredembodiments increasing the local density is done by applying pressureonto the predetermined sub-regions of the polymeric shell.

According to still further features in the described preferredembodiments increasing the local density is done by pressing a pluralityof rollers, spaced apart from one another, onto the polymeric shell.

According to still further features in the described preferredembodiments increasing the local density is done by pressing a spiralpattern onto the polymeric shell.

According to still further features in the described preferredembodiments increasing said local density is done by pressing a rigidirregular pattern onto said polymeric shell.

According to still further features in the described preferredembodiments the method further comprising mixing the liquefied polymerwith a charge control agent prior to the step of dispensing.

According to still further features in the described preferredembodiments the method further comprising reducing non-uniformities inan electric field generated between the precipitation electrode and thedispenser.

According to still further features in the described preferredembodiments reducing non-uniformities in the electric field is done bypositioning a subsidiary electrode, being at a second potential relativeto the precipitation electrode, close to the precipitation electrode.

According to still further features in the described preferredembodiments the method further comprising controlling fiber orientationof the tubular structure formed upon the precipitation electrode.

According to still further features in the described preferredembodiments controlling fiber orientation is done by positioning asubsidiary electrode, being at a second potential relative to theprecipitation electrode, close to the precipitation electrode.

According to still further features in the described preferredembodiments the method further comprising moving the subsidiaryelectrode along the precipitation electrode.

According to still further features in the described preferredembodiments the method further comprising tilting the subsidiaryelectrode at angle with respect to the precipitation electrode.

According to still further features in the described preferredembodiments the method further comprising entangling at least a portionof a plurality of polymer fibers dispensed by the dispenser, so as toprovide at least one polymer fiber bundle moving in a direction of theprecipitation electrode.

According to still further features in the described preferredembodiments the step of entangling comprises providing an electric fieldhaving at least one rotating component around a first axis definedbetween the precipitation electrode and the dispenser.

According to still further features in the described preferredembodiments providing an electric field having at least one rotatingcomponent, is done by providing a system of electrodes, being laterallydisplaced from the dispenser, being at a third potential relative to theprecipitation electrode and operable to provide a time-dependentelectric field.

According to still further features in the described preferredembodiments providing an electric field having at least one rotatingcomponent, is done by providing at least one rotating electrode, beinglaterally displaced from the dispenser, being at a third potentialrelative to the precipitation electrode and operable to rotate aroundthe first axis.

According to still further features in the described preferredembodiments the method further comprising independently moving thedispenser and the at least one rotating electrode along theprecipitation electrode.

According to still further features in the described preferredembodiments the method further comprising synchronically moving thedispenser and the at least one rotating electrode along theprecipitation electrode.

According to still further features in the described preferredembodiments the precipitation electrode comprises at least one rotatingmandrel.

According to still further features in the described preferredembodiments the dispenser comprises a mechanism for forming a jet of theis liquefied polymer.

According to still further features in the described preferredembodiments the mechanism for forming a jet of the liquefied polymerincludes a dispensing electrode.

According to still further features in the described preferredembodiments the subsidiary electrode is of a shape selected from thegroup consisting of a plane, a cylinder, a torus and a wire.

According to yet another aspect of the present invention there isprovided a tubular structure, comprising at least one layer ofelectrospun polymer fibers, each layer having a predetermined porosityand an alternating density in a longitudinal direction of the tubularstructure.

According to further features in preferred embodiments of the inventiondescribed below, the tubular structure is sized and having properties soas to serve as a vascular prosthesis.

According to still another aspect of the present invention there isprovided a vascular prosthesis, comprising at least one layer ofelectrospun polymer fibers, each layer having a predetermined porosityand an alternating density in a longitudinal direction of the vascularprosthesis.

According to further features in preferred embodiments of the inventiondescribed below, the polymer is a biocompatible polymer.

According to still further features in the described preferredembodiments the polymer is selected from the group consisting ofpolyethylene terephtalat and polyurethane.

According to still further features in the described preferredembodiments said at least one layer includes at least one drugincorporated therein, for delivery of the at least one drug into a bodyvasculature during or after implantation of the vascular prosthesiswithin the body vasculature.

According to still further features in the described preferredembodiments the electrospun polymer fibers are a combination of abiodegradable polymer and a biostable polymer.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing an electrospinning apparatusand method capable of improving kinking resistance of tubular structuresproduced thereby.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1 is a schematic illustration of a prior art electrospinningapparatus;

FIG. 2 is a schematic illustration of an apparatus for forming a tubularstructure from a liquefied polymer, according to one embodiment of thepresent invention;

FIG. 3 a is a mechanism for increasing a local density of the polymericshell embodied as a plurality of rollers, according to the presentinvention;

FIG. 3 b is the mechanism for increasing a local density of thepolymeric shell embodied as a spiral pattern, according to the presentinvention;

FIG. 3 c is the mechanism for increasing a local density of thepolymeric shell embodied as a rigid irregular pattern, according to thepresent invention;

FIG. 4 is a schematic illustration of the apparatus for forming atubular structure further comprising a subsidiary electrode, accordingto the present invention;

FIG. 5 is a schematic illustration of the apparatus for forming atubular structure further comprising a mechanism for intertwining atleast a portion of the polymer fibers, according to the presentinvention;

FIG. 6 is a schematic illustration of the intertwining mechanism in theform of a plurality of stationary electrodes, according to the presentinvention;

FIG. 7 is a schematic illustration of the intertwining mechanism in theform of at least one rotating electrodes, according to the presentinvention.

FIG. 8 a is a tubular structure having toroidal pattern of high densityregions, according to the present invention;

FIG. 8 b is a tubular structure having spiral-like pattern of highdensity regions, according to the present invention; and

FIG. 8 c is a tubular structure having irregular pattern of high densityregions, according to the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of a method and apparatus for forming a tubularstructure which can be for example an artificial blood vessel.

Specifically, the present invention can be used to fabricate a tubularstructure having an improved kinking resistance.

For purposes of better understanding the present invention, asillustrated in FIGS. 2-8 of the drawings, reference is first made to theconstruction and operation of a conventional (i.e., prior art)electrospinning apparatus as illustrated in FIG. 1.

FIG. 1 illustrates an apparatus for manufacturing a non-woven materialusing electrospinning, which is referred to herein as apparatus 10.

Apparatus 10 includes a dispenser 12 which can be, for example, areservoir provided with one or more capillary apertures 14. Dispenser 12serves for storing the polymer to be spun in a liquid form, i.e.,dissolved or melted. Dispenser 12 is positioned at a predetermineddistance from a precipitation electrode 16. Precipitation electrode 16serves for forming the tubular structure thereupon. Precipitationelectrode 16 is typically manufactured in the form of a mandrel or anyother substantially cylindrical structure. Precipitation electrode 16 isrotated by a mechanism such that a tubular structure is formed whencoated with the polymer. Dispenser 12 is typically grounded, whileprecipitation electrode 16 is connected to a source of high voltage,preferably of negative polarity, thus forming an electric field betweendispenser 12 and precipitation electrode 16. Alternatively,precipitation electrode 16 can be grounded while dispenser 12 isconnected to a source of high voltage, preferably with positivepolarity.

To generate a tubular structure, a liquefied polymer (e.g., meltedpolymer or dissolved polymer) is extruded, for example under the actionof hydrostatic pressure, or using a pump (not shown in FIG. 1), throughcapillary apertures 14 of dispenser 12. As soon as meniscus of theextruded liquefied polymer forms, a process of solvent evaporation orcooling starts, which is accompanied by the creation of capsules with asemi-rigid envelope or crust. An electric field, occasionallyaccompanied by a unipolar corona discharge in the area of dispenser 12,is generated by the potential difference between dispenser 12 andprecipitation electrode 16. Because the liquefied polymer possesses acertain degree of electrical conductivity, the above-described capsulesbecome charged. Electric forces of repulsion within the capsules lead toa drastic increase in hydrostatic pressure. The semi-rigid envelopes arestretched, and a number of point micro-ruptures are formed on thesurface of each envelope leading to spraying of ultra-thin jets ofliquefied polymer from dispenser 12.

Under the effect of a Coulomb force, the jets depart from dispenser 12and travel towards the opposite polarity electrode, i.e., precipitationelectrode 16. Moving with high velocity in the inter-electrode space,the jet cools or solvent therein evaporates, thus forming fibers whichare collected on the surface of precipitation electrode 16.

Tubular structure formed in a typical electrospinning process (e.g., asemployed by apparatus 10 ), lack sufficient kinking resistance andfurther reinforcement of the final product is often necessary to supportthe lumen of the tubular structure while bending. According to thepresent invention there is provided an apparatus for forming a tubularstructure having an intrinsic kinking resistance (i.e. withoutadditional supporting elements).

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Referring now again to the drawings, FIG. 2 illustrates an apparatus,generally referred to herein as apparatus 20, for forming a tubularstructure from a liquefied polymer according to the teachings of thepresent invention. Apparatus 20 includes a dispenser 21 for dispensingthe liquefied polymer, and a precipitation electrode 22 being at a firstpotential relative to dispenser 21. Precipitation electrode 22 servesfor generating a polymeric shell thereupon. Apparatus 20 furtherincludes a mechanism 26 for increasing a local density of the polymericshell in a plurality of predetermined sub-regions of the polymericshell, thereby to provide a tubular structure having an alternatingdensity in a longitudinal direction.

Dispenser 21 is preferably at a first potential relative to dispenser21. According to a preferred embodiment of the present invention,dispenser 21 may be operable to move along precipitation electrode 22,so as to ensure complete or predetermined covering of precipitationelectrode 22. In addition, precipitation electrode 22 is preferablyoperable to rotate around a longitudinal axis.

The operations of dispenser 21 and precipitation electrode 22 to form apolymeric shell are similar to the operations of dispenser 12 andprecipitation electrode 16 of apparatus 10, as detailed hereinabove. Theposition and size of, and the material from which mechanism 26 is madeof are all selected to ensure that precipitation electrode 22 shieldsmechanism 26, hence minimize any change in the electric field due to thenearby presence mechanism 26. Mechanism 26 is preferably grounded.

According to a preferred embodiment of the present invention, mechanism26 may be any device capable of locally increasing the density of thepolymer fibers. Specifically, mechanism 26 may be a pressing mechanism,so that the polymer fibers, being pressed by mechanism 26, areefficiently stuck together forming a rigid and denser three-dimensionalstructure. Such condensation results in a certain reduction ofelectrical resistance in the condensed area and a correspondingintensification of fiber deposition thereat in subsequentelectrospinning steps.

Reference is now made to FIGS. 3 a-c showing three alternatives formechanism 26. In FIG. 3 a, mechanism 26 is embodied as a plurality ofrollers 32 spaced apart from one another. Rollers 32 are connected to anaxle 34 and operable to freely rotate about axle 34. In FIG. 3 b,mechanism 26 is embodied as a rigid spiral pattern 36, operable torotate about a longitudinal axis 38. In FIG. 3 c, mechanism 26 isembodied as a rigid irregular pattern 37, operable to rotate about alongitudinal axis 38.

In the preferred embodiment in which mechanism 26 is a spiral,longitudinal forces are present between mechanism 26 and precipitationelectrode 22. Hence, according to a preferred embodiment of the presentinvention, mechanism 26 may be operable to move along longitudinal axis38, so as to prevent smearing of the compressed sub-regions ofprecipitation electrode 22. It should be understood, that the length ofmechanism 26 is chosen so that a predetermined length of the producedtubular shell is in contact with mechanism 26.

The rotation of mechanism 26 may be either free rotation or forcedrotation, by the use of a rotating device 39. According to a preferredembodiment of the present invention, mechanism 26 may be either ininactive mode, i.e. detached from precipitation electrode 22, or inactive mode i.e. when mechanism 26 (either embodied as rollers 32 or asspiral pattern 36) is pressed against precipitation electrode 22.Whether or not mechanism 26 is connected to rotating device 39, whenmechanism 26 is in its active mode, the relative transverse velocitybetween precipitation electrode 22 and mechanism 26 should besynchronized to substantially zero, so as to ensure a rolling withoutsliding motion. Once mechanism 26 is pressed onto precipitationelectrode 22, denser three dimensional patterns start to appear on thesurface of the formed tubular structure, which patterns depend on theshape and size of mechanism 26 as shown in FIGS. 3 a-c.

Apparatus 20 described hereinabove can be efficiently used forgenerating tubular structures upon a precipitation electrode having orlarge radius of curvature. However, when using a precipitation electrodebeing at least partially with small radius of curvature, the orientationof the electric field maximal strength vector is such that precipitationelectrode 22 is coated coaxially by the fibers. Thus, small diameterproducts, may exhibit limited radial strength.

In cases where precipitation electrode 22 comprises sharp edges and/orvariously shaped and sized recesses, the electric field magnitude in thevicinity of precipitation electrode 22 may exceed the air electricstrength (about 30 kV/cm), and a corona discharge may develop in thearea of precipitation electrode 22. The effect of corona dischargedecreases the coating efficiency of the process as further detailedherein.

Corona discharge initiation is accompanied by the generation of aconsiderable amount of air ions having opposite charge sign with respectto the charged fibers. Since an electric force is directed with respectto the polarity of charges on which it acts, theses ions start to moveat the opposite direction to fibers motion i.e., from precipitationelectrode 22 towards dispenser 24. Consequently, a portion of these ionsgenerate a volume charge (ion cloud), non-uniformly distributed in theinter-electrode space, thereby causing electric field lines to partiallyclose on the volume charge rather than on precipitation electrode 22.Moreover, the existence of an opposite volume charges in theinter-electrode space, decreases the electric force on the fibers, thusresulting in a large amount of fibers accumulating in theinter-electrode space. Such an effect may lead to a low-efficiencyprocess of fiber coating, and may even result in a total inability offibers to be collected upon precipitation electrode 22.

The present invention successfully addresses both of the above problems,by providing a subsidiary electrode within apparatus 20, so as tocontrol the electric field. Specifically, a subsidiary electrode mayeither substantially decreases non-uniformities in the electric fieldand/or provides for controlled fiber orientation upon deposition.

Reference is now made to FIG. 4, which depicts another preferredembodiment of the present invention, which may be employed forfabricating tubular structures having a small diameter and/orintricate-profile. Hence, apparatus 20 may further comprise a subsidiaryelectrode 46 which is kept at a second potential difference relative todispenser 21. Subsidiary electrode 46 serves for controlling thedirection and magnitude of the electric field in the inter-electrodespace and as such, subsidiary electrode 46 can be used to control theorientation of polymer fibers deposited on precipitation electrode 22.In some embodiments, subsidiary electrode 46 serves as a supplementaryscreening electrode. Broadly stated, use of screening results indecreasing the coating precipitation factor, which is particularlyimportant upon precipitation electrodes having at least a section ofsmall radii of curvature.

According to a preferred embodiment of the present invention the size,shape, position and number of subsidiary electrode 46 is selected so asto maximize the coating precipitation factor, while minimizing theeffect of corona discharge in the area of precipitation electrode 22and/or so as to provide for controlled fiber bundles orientation upondeposition. Thus, subsidiary electrode 46 may be fabricated in a varietyof shapes each serving a specific purpose. Electrode shapes which can beused with apparatus 20 of the present invention include, but are notlimited to, a plane, a cylinder, a torus a rod, a knife, an arc or aring.

According to a presently preferred embodiment of the invention,subsidiary electrode 46 may be operable to move along precipitationelectrode 22. Such longitudinal motion may be in use when enhancedcontrol over fiber orientation is required. The longitudinal motion ofsubsidiary electrode 46 may be either independent or synchronized withthe longitudinal motion of dispenser 21. Subsidiary electrode 46 mayalso be tilted through an angle of 45°-90° with respect to alongitudinal axis of precipitation electrode 22, which tilting may beused to provide for controlled fiber-bundle orientation upon deposition,specifically, large angles result in predominant polar (transverse)orientation of bundles.

Depending on the use of the tubular structure formed by apparatus 20, itmay be required to enhance the strength and/or elasticity, both in aradial direction and in an axial direction, of the final product. Thisis especially important when the tubular structure is to be used inmedical applications, where a combination of high elasticity, strength,small thickness, porosity, and low basis weight are required. Accordingto a preferred embodiment of the present invention the strength of thetubular structure may be significantly enhanced, by employing anadditional electric field having at least one rotating element, asdescribed herein.

Referring to FIG. 5, apparatus 20 further includes a mechanism 52 forintertwining at least a portion of the polymer fibers, so as to provideat least one polymer fiber bundle moving in a direction of precipitationelectrode 22. Mechanism 52 may include any mechanical and/or electroniccomponents which are capable for intertwining the polymer fibers “on thefly”, as is further detailed hereinunder, with reference to FIGS. 6-7.

Thus, FIG. 6 illustrates one embodiment of the present invention inwhich mechanism 52 includes a system of electrodes being laterallydisplaced from dispenser 21 and preferably at a third potential relativeto dispenser 21. According to a preferred embodiment of the presentinvention the system of electrodes may be constructed in any way knownin the art for providing an electric field rotating around a first axis56 defined between said dispenser and said precipitation electrode.

For example, as shown in FIG. 6, the system of electrodes may includetwo or more stationary electrodes 62, connected to at least one powersource 64, so that the potential difference between electrodes 62 andprecipitation electrode 22 (and between electrodes 62 and dispenser 21 )varies in time. Power sources 64, being electronically communicatingwith each other so as to synchronize a relative phase between electrodes62. Hence, each of stationary electrodes 62 generates a time-dependentelectric field having a constant direction. The electronic communicationbetween power sources 64 ensures that the sum of all (time-dependent)field vectors is rotating around first axis 56.

Reference is now made to FIG. 7, in which mechanism 52 is manufacturedas at least one rotating electrode 72, operable to rotate around firstaxis 56. Rotating electrode 72, being at a third potential relative todispenser 21, generates an electric field, the direction of whichfollows the motion of rotating electrode 72, hence an electric fieldhaving at least one rotating component is generated.

According to the presently preferred embodiment of the invention, inoperation mode of apparatus 20, the liquefied polymer is dispensed bydispenser 24, and then, subjected to the electric field, moves in theinter-electrode space. The electric field in the inter-electrode spacehas at least one rotating component around first axis 56 (generated bythe potential difference between mechanism 52 and precipitationelectrode 22 ) and a stationary electric field (generated by thepotential difference between dispenser 21 and precipitation electrode 22). Hence, in addition to the movement in the direction of precipitationelectrode 22, the jets of liquefied polymer, under the effect of therotating component of the electric field twist around first axis 56. Therotation frequency may be controlled by a suitable choice ofconfiguration for the system of electrodes, as well as on the value ofthe potential differences employed.

At a given time, the effect of the rotating component of the electricfield on the jets neighboring mechanism 52 is larger than the effect onthe jets which are located far from mechanism 52. Hence, thetrajectories of the fibers start crossing one another, resulting inphysical contacts and entanglement between fibers prior toprecipitation.

Thus, apparatus 20 generates higher-order formations of fiber bundlesfrom the elementary fibers in the spray jet. The structure of the formedfiber bundles is inhomogeneous and depends on the distance of the fiberbundle from mechanism 52. Specifically, the extent of fiber twisting andinterweaving, and the amount of fibers in the bundle, is an increasingfunction of the distance from mechanism 52. During the motion of thebundles in the inter-electrode space, they may also intertwine with oneanother, forming yet thicker bundles.

The bundles, while formed, continue to move in the inter-electrodespace, directed to precipitation electrode 22, forming the tubularstructure thereupon. The formed material has three-dimensional reticularstructure, characterized by a large number of sliding contacts betweenfibers. Such contacts significantly increase the strength of thematerial, due to friction forces between fibers. The ability of fibersfor mutual displacement increases the elasticity of the non-wovenmaterial under loading.

According to another aspect of the present invention there is provided amethod for of forming a tubular structure from a liquefied polymer. Themethod comprises the following steps which may be executed, for example,using apparatus 20. Hence, in a first step, the liquefied polymer isdispensed via electrospinning from a dispenser in a direction of aprecipitation electrode, thus forming a plurality of polymer fibersprecipitated onto the precipitation electrode, hence providing apolymeric shell. In a second step, a local density of the polymericshell is increased in a plurality of predetermined sub-regions of thepolymeric shell. These steps may be subsequent or be implementedsubstantially simultaneously.

According to a preferred embodiment of the present invention, the methodmay further comprise the step of entangling at least a portion of thepolymer fibers, so as to provide at least one polymer fiber bundlemoving in the direction of the precipitation electrode. In addition, themethod may further comprise a step of controlling fiber and/or fiberbundles orientation of the tubular structure formed upon theprecipitation electrode. Still in addition, the method may comprisereducing undesired non-uniformities in the electric field in thevicinity of the precipitation electrode. The steps of controlling fiberand/or fiber bundles orientation and of reducing non-uniformities in theelectric field may be performed by the use of a subsidiary electrode, asdetailed hereinabove, with reference to FIG. 4.

It is to be understood, that the second step of the invention isperformed, whether or not the above additional steps of entangling,controlling fiber orientation and reducing electric fieldnon-uniformities have been employed. Furthermore, each of the additionalsteps may be employed independently.

According to a preferred embodiment of the present invention, the methodmay iteratively proceed, so that a multilayer tubular structure isformed. Specifically, once a first layer is formed on the precipitationelectrode, the second step of the method is employed so that the firstlayer of the tubular structure is characterized by an alternatingdensity in a longitudinal direction. The second step may be employed, byswitching mechanism 26 into active mode, e.g., by moving axle 34 closerto the precipitation electrode so that rollers 32 are pressed onto thefirst layer.

In a subsequent iteration, mechanism 26 is switched into an inactivemode (e.g., by moving axle 34 sufficiently far from the precipitationelectrode) and the electrospinning step is repeated to provide anadditional layer.

Thus, a multilayer structure is formed, wherein each layer is providedwith a plurality of higher density sections. Reference is now made toFIGS. 8 a-c, showing three alternatives of the higher density patternsformed on a specific layer (for example the first layer) of tubularstructure 82. Hence, FIG. 8 a illustrates toroidal high density patternsformed on tubular structure 82. Such high density patterns may beprovided for example by using a plurality of rollers as the mechanismfor increasing a local density, as detailed hereinabove, and illustratedin FIG. 3 a. FIG. 8 b illustrates a high density pattern which may beformed by using spiral pattern as a pressing mechanism, as detailedhereinabove, and illustrated in FIG. 3 b. Finally, FIG. 3 c illustratesan irregular pattern of high density formed onto the surface of tubularstructure 82, which may be patterned by a pressing mechanism shown andin FIG. 3 c and described hereinabove.

It should be appreciated that the high density regions on the outersurface the layers of tubular structure 82, may have any predeterminedpattern (depending on the application in which tubular structure 82 isto be used), and are not limited to those shown in FIGS. 8 a-c.

The tubular structure, which may serve in variety of industrial andmedical application, is capable to withstand kinking collapse whilemaintaining a predetermined porosity as well as inner and/or outersurface smoothness. A typical width of the toroidal sections may rangefrom 0.5 to 3 mm.

According to a preferred embodiment of the present invention, themultilayer structure may be sized and having properties so as to serveas a vascular prosthesis. One advantage of a vascular prosthesis,fabricated in accordance to a preferred embodiment of the presentinvention, is that drug delivery into a body vasculature can beperformed during or after implantation of the vascular prosthesis withinthe body vasculature. Thus, each the layers may incorporate at least onedrug therein, for delivery into body vasculature by, for example, a slowrelease mechanism. It is appreciated that the drug incorporated, as wellas the concentration and method of incorporation into the prosthesis isin accordance with the type of vessel being replaced, and with theparticular pathology of the patient.

According to a preferred embodiment of the present invention, theliquefied polymer loaded into dispenser 21 may be, for examplepolyurethane, polyester, polyolefin, polymethylmethacrylate, polyvinylaromatic, polyvinyl ester, polyamide, polyimide, polyether,polycarbonate, polyacrilonitrile, polyvinyl pyrrolidone, polyethyleneoxide, poly (L-lactic acid), poly (lactide-CD-glycoside),polycaprolactone, polyphosphate ester, poly (glycolic acid), poly(DL-lactic acid), and some copolymers. Biolmolecules such as DNA, silk,chitozan and cellulose may also be used in mix with synthetic polymers.Improved charging of the polymer may also be required. Improved chargingis effected according to the present invention by mixing the liquefiedpolymer with a charge control agent (e.g., a dipolar additive) to form,for example, a polymerdipolar additive complex which apparently betterinteracts with ionized air molecules formed under the influence of theelectric field. The charge control agent is typically added in the gramsequivalent per liter range, say, in the range of from about 0.001 N toabout 0.1 N, depending on the respective molecular weights of thepolymer and the charge control agent used.

U.S. Pat. Nos. 5,726,107; 5,554,722; and 5,558,809 teach the use ofcharge control agents in combination with polycondensation processes inthe production of electret fibers, which are fibers characterized in apermanent electric charge, using melt spinning and other processesdevoid of the use of a precipitation electrode. A charge control agentis added in such a way that it is incorporated into the melted orpartially melted fibers and remains incorporated therein to provide thefibers with electrostatic charge which is not dissipating for prolongedtime periods, say weeks or months. In a preferred embodiment of thepresent invention, the charge control agent transiently binds to theouter surface of the fibers and therefore the charge dissipates shortlythereafter. This is because polycondensation is not exercised at allsuch that the chemical interaction between the agent and the polymer isabsent, and further due to the low concentration of charge control agentemployed. The resulting tubular structure is therefore, if so desired,substantially charge free.

Suitable charge control agents include, but are not limited to, mono-and poly-cyclic radicals that can bind to the polymer molecule via, forexample, —C═C—, ═C—SH— or —CO—NH— groups, including biscationic amides,phenol and uryl sulfide derivatives, metal complex compounds,triphenylmethanes, dimethylmidazole and ethoxytrimethylsians.

Additional objects, advantages, and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following example, which is not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present invention as delineated hereinabove and as claimed in theclaims section below finds experimental support in the followingexample.

EXAMPLE

Reference is now made to the following example, which together with theabove descriptions, illustrate the invention in a non limiting fashion.

Tubular structures, 6 mm in diameter and 200 mm in length weremanufactured.

A polyurethane of Carbotan 3595 blend was purchased from The PolymerTechnology Group Incorporated. This polymer was provided with aromaticurethane hard segment, polycarbonate and silicone co-soft segments andsurface-modifying end groups. Silicone-urethane copolymers demonstrate acombination of high mechanical properties with oxidative stability, lowrate of hydrolytic degradation biostabillity and tromboresistance. Inaddition, this polymer is characterized by a high fiber forming ability.

A rod, 6 mm in diameter and 300 mm in length was used as a precipitationelectrode, and its central 200 mm portion was coated at ambienttemperature (24° C.). The precipitation electrode was rotated at anangular velocity of 100 rpm.

A spinneret was used as the dispensing electrode, the inner diameter ofthe spinneret was 0.5 mm, and the flow-rate was 3 ml/h. The dispensingelectrode was grounded while the precipitation electrode was kept at apotential of −50 kV, relative to the dispensing electrode.

The dispensing electrode was positioned 35 cm from the precipitationelectrode. Reciprocal motion of the dispensing electrode was enabledalong the mandrel longitudinal axis at a frequency of 5 motions perminute.

An axel connected to a plurality of rollers, spaced apart from oneanother, was used as a mechanism for increasing a local density. Thespacing between the rollers was 1.2 mm, and the width of each roller was0.8 mm.

Four tubular structures were manufactured according to the teaching ofthe present invention, for each tubular structure a different pressureof the rollers onto the mandrel was applied. The resulting thicknessesof the compressed sub-regions were: 0.5, 0.6, 0.8 and 0.9. In addition,for comparison, a tubular structure was manufactured employingconventional electrospinning process without the step of increasinglocal densities.

In all the experiments, the parameters of the electrospinning processwere identical, except for the pressure of the rollers on the mandrel.

The manufactured tubular structures were subjected to bending tests soas to compare the kinking resistance of the final product, as a functionof the of the compressed sub-regions thicknesses. In addition, globaland local measurements of the basis weight were performed for each ofthe tubular structures.

Table 1 lists some comparative characteristics of the tubular structuresproduced by a conventional electrospinning technique by the teachings ofthe present invention.

TABLE 1 Wall thickness [mm] Basis weight [g/m²] Critical Non- Non-bending Compressed compressed Compressed compressed radius sub-regionsub-region Web sub-region sub-region [mm] — 0.6 150 — — 25.0 0.5 0.6 200250 160 7.0 0.6 0.6 290 430 150 14.0 0.8 0.6 280 400 150 17.0 0.9 0.8420 650 220 11.0

As can be seen from Table 1, the existence of compressed sub-regions onthe wall of the tubular structure provides relatively heavy sub-regionsof the structure. In some experiments, intensification of fiberdeposition upon the precipitation electrode in the compressedsub-regions has been observed. This is shown at the bottommost two rowsof Table 1, where the wall thickness at the compressed sub-regions islarger than the “original” wall thickness (i.e. at the non-compressedsub-regions). The observed phenomenon is due to a reduction ofelectrical resistance in the compressed sub-regions.

These compressed sub-regions, significantly increase the ability of thestructure to bend. The thinner the thickness of the wall at thecompressed subregion, the larger is the kinking resistance of thestructure.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1. An apparatus for forming a tubular structure having improved kinkingresistance from a liquefied polymer, the apparatus comprising: (a) adispenser for dispensing the liquefied polymer; (b) a precipitationelectrode being at a first potential relative to said dispenser, saidprecipitation electrode being designed and constructed for generating afibrous polymeric shell thereupon; and (c) a pressing mechanism forincreasing a local density of said polymeric shell in a plurality ofpredetermined sub-regions of said polymeric shell, thereby to provide atubular structure having an alternating density in a longitudinaldirection, wherein the alternating density regions formed comprisescompressed sub-regions and non-compressed sub-regions in a longitudinaldirection of the tubular structure, wherein a basis weight of saidcompressed sub-regions is larger than a basis weight of saidnon-compressed sub-regions.
 2. The apparatus of claim 1, wherein saidpressing mechanism for increasing said local density comprises aplurality of rollers spaced apart from one another.
 3. The apparatus ofclaim 1, wherein said pressing mechanism for increasing said localdensity comprises a spiral pattern.
 4. The apparatus of claim 1, whereinsaid pressing mechanism for increasing said local density comprises arigid irregular pattern.
 5. The apparatus of claim 1, wherein saidprecipitation electrode comprises at least one rotating mandrel.
 6. Theapparatus of claim 1, wherein said dispenser is operable to move alongsaid precipitation electrode.
 7. The apparatus of claim 3, wherein saiddispenser comprises a mechanism for forming ajet of the liquefiedpolymer.
 8. The apparatus of claim 7, wherein said mechanism for formingajet of the liquefied polymer includes a dispensing electrode.
 9. Theapparatus of claim 1, further comprising a reservoir for holding theliquefied polymer.
 10. The apparatus of claim 1, further comprising asubsidiary electrode being at a second potential relative to saiddispenser, and being for modifying an electric field generated betweensaid precipitation electrode and said dispenser.
 11. The apparatus ofclaim 10, wherein said subsidiary electrode serves for reducingnon-uniformities in said electric field.
 12. The apparatus of claim 10,wherein said subsidiary electrode serves for controlling fiberorientation of the tubular structure formed upon said precipitationelectrode.
 13. The apparatus of claim 10, wherein said subsidiaryelectrode is of a shape selected from the group consisting of a plane, acylinder, a torus and a wire.
 14. The apparatus of claim 10, whereinsaid subsidiary electrode is operative to move along said precipitationelectrode.
 15. The apparatus of claim 10, wherein said subsidiaryelectrode is tilted at angle with respect to said precipitationelectrode.
 16. An apparatus for forming a tubular structure havingimproved kinking resistance from a liquefied polymer, the apparatuscomprising: (a) a dispenser for dispensing the liquefied polymer; (b) aprecipitation electrode being at a first potential relative to saiddispenser, said precipitation electrode being designed and constructedfor generating a fibrous polymeric shell thereupon; (c) a pressingmechanism for increasing a local density of said polymeric shell in aplurality of predetermined sub-regions of said polymeric shell, therebyto provide a tubular structure having an alternating density in alongitudinal direction; wherein the alternating density regions formedcomprises compressed sub-regions and non-compressed sub-regions in alongitudinal direction of the tubular structure, wherein a basis weightof said compressed sub-regions is larger than a basis weight of saidnon-compressed sub-regions and (d) a system of electrodes, beinglaterally displaced from said dispenser, being at a third potentialrelative to said dispenser and capable of providing an electric fieldhaving at least one rotating component around a first axis definedbetween said dispenser and said precipitation electrode, forintertwining at least a portion of a plurality of polymer fibersdispensed by said dispenser, so as to provide at least one polymer fiberbundle moving in a direction of said precipitation electrode.
 17. Amethod of forming a tubular structure having improved kinking resistancefrom a liquefied polymer, the method comprising: (a) viaelectrospinning, dispensing the liquefied polymer from a dispenser in adirection of a precipitation electrode, hence forming fibrous polymericshell; and (b) applying pressure onto predetermined sub-regions of saidpolymeric shell such as to increase a local density of said polymericshell in said plurality of predetermined sub-regions, thereby providinga tubular structure having an alternating density in a longitudinaldirection (b), wherein the alternating density regions formed comprisescompressed sub-regions and non-compressed sub-regions in a longitudinaldirection of the tubular structure, wherein a basis weight of saidcompressed sub-regions is larger than a basis weight of saidnon-compressed sub-regions.
 18. A tubular structure having improvedkinking resistance, comprising at least one layer of electrospun polymerfibers, each layer having a predetermined porosity and an alternatingdensity characterized by compressed sub-regions and non-compressedsub-regions in a longitudinal direction of the tubular structure,wherein a basis weight of said compressed sub-regions is larger than abasis weight of said non-compressed sub-regions.
 19. The apparatus ofclaim 16, wherein said mechanism for increasing said local densitycomprises a plurality of rollers spaced apart from one another.
 20. Theapparatus of claim 16, wherein said mechanism for increasing said localdensity comprises a spiral pattern.
 21. The apparatus of claim 16,wherein said mechanism for increasing said local density comprises arigid irregular pattern.
 22. The apparatus of claim 16, furthercomprising a subsidiary electrode being at a second potential relativeto said dispenser, and being for modifying an electric field generatedbetween said precipitation electrode and said dispenser.
 23. Theapparatus of claim 22, wherein said subsidiary electrode serves forreducing non-uniformities in said electric field.
 24. The apparatus ofclaim 22, wherein said subsidiary electrode serves for controlling fiberorientation of the tubular structure formed upon said precipitationelectrode.
 25. The apparatus of claim 22, wherein said subsidiaryelectrode is of a shape selected from the group consisting of a plane, acylinder, a torus and a wire.
 26. The apparatus of claim 22, whereinsaid subsidiary electrode is operative to move along said precipitationelectrode.
 27. The apparatus of claim 22, wherein said subsidiaryelectrode is tilted at angle with respect to said precipitationelectrode.
 28. The method of claim 17, further comprising independentlyrepeating said steps (a) and (b) at least once.
 29. The method of claim17, wherein said increasing said local density is done by pressing aplurality of rollers, spaced apart from one another, onto said polymericshell.
 30. The method of claim 17, wherein said increasing said localdensity is done by pressing a spiral pattern onto said polymeric shell.31. The method of claim 17, wherein said increasing said local densityis done by pressing a rigid irregular pattern onto said polymeric shell.32. The method of claim 17, further comprising reducing non-uniformitiesin an electric field generated between said precipitation electrode andsaid dispenser.
 33. The method of claim 32, wherein said reducingnon-uniformities in said electric field is done by positioning asubsidiary electrode close to said precipitation electrode.
 34. Themethod of claim 17, further comprising controlling fiber orientation ofthe tubular structure formed upon said precipitation electrode.
 35. Themethod of claim 34, wherein said controlling fiber orientation is doneby positioning a subsidiary electrode close to said precipitationelectrode.
 36. The tubular structure of claim 18, capable ofwithstanding kinking collapse when bent at a bending radius which islower than 25 mm.
 37. The tubular structure of claim 18, wherein saidbasis weight of said compressed sub-regions is at least 250 g/m² andsaid basis weight of said non-compressed sub-regions is not higher than220 g/m².